KUO, SHENG CHU,郭盛助,郭盛助,LEE, KUO-HSIUNG,李国雄,李國雄,HUANG, LI JIAU,黄丽娇,黃麗嬌,WU, TIAN SHUNG,吴天赏,吳天賞,LIU, CHIN YU,刘晋育,劉晉育,CHENG, YUNG YI,郑雍怡,鄭雍怡,CHANG, LING CHU,张玲菊,張玲菊,CHOU, LI CHEN,周立琛,周立琛,HUANG, CHI HUNG,黄
申请号：
TW103115220
公开号：
TW201444837A
申请日:
2014.04.28
申请国别(地区):
TW
年份:
2014
代理人:
摘要：
In order to search for new antitumor drug candidates from 2-arylnaphthyridin-4-ones (ANs), we have designed and synthesized a series of 3’-hydroxy or 6-hydroxy derivatives of ANs. Following the antitumor activity screening, most of these compounds were found to exhibit significant activity. Among them, 2-(3-hydroxyphenyl)-5-methyl-1,8-naphthyridin-4(1H)-one (67) was the most promising. In a preliminary action mechanism study, the treatment of Hep3B hepatoma cells with compound 67 reveals that its mechanism of action is affect on microtubule and metastasis-related proteins. Then, the corresponding phosphate prodrug (86) of compound 67 was tested against Hep3B xenograft nude mice model for antitumor activity.為了從2-芳基萘啶-4-酮類(ANs)搜尋出新型抗腫瘤藥物候選物,我們已設計及合成一系列ANs的3’-羥基或6-羥基衍生物。在抗腫瘤活性篩選後,已發現這些化合物大部分具有明顯的活性。在此當中,2-(3-羥基苯基)-5-甲基-1,8-萘啶-4(1H)-酮(67)係最有前途。在初步作用機制研究中,以化合物67治療Hep3B肝細胞瘤細胞顯露出其作用機制係受微管及轉移相關蛋白質影響。然後,測試化合物67之相應磷酸鹽前藥體(86)對抗Hep3B異種移植裸小鼠模型之抗腫瘤活性。
